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海马体集合记忆相关表观基因组和转录组相互作用
作者:小柯机器人 发布时间:2020/10/8 22:33:02

美国麻省理工学院Asaf Marco课题组取得一项新突破。他们研究发现在海马体集合中记忆形成和记忆中映射表观基因组和转录组相互作用。2020年10月5日出版的国际知名学术期刊《自然-神经科学》发表了这一成果。

在这项研究中,他们在小鼠中使用了一种依赖于活动的标记系统,以确定在记忆形成和记忆的整个生命周期中字母细胞的表观遗传状态、三维(3D)基因组结构和转录环境。他们的发现表明,记忆编码导致表观遗传启动事件,其特征在于增强子的可及性增加,而没有相应的转录变化。记忆巩固随后导致大染色质片段的空间重组和启动子-增强子相互作用。

最后,通过重新激活,字母神经元使用从头远程相互作用亚群,其中引发的增强子与它们各自的启动子接触,以上调与突触区室中局部蛋白质翻译有关的基因。总的来说,他们的工作阐明了整个海马字母集合体在记忆形成和记忆过程中的转录和表观基因组情况。

据悉,表观基因组和3D基因组结构正在成为动态调节神经元功能所需的不同转录程序的关键因素。

附:英文原文

Title: Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble

Author: Asaf Marco, Hiruy S. Meharena, Vishnu Dileep, Ravikiran M. Raju, Jose Davila-Velderrain, Amy Letao Zhang, Chinnakkaruppan Adaikkan, Jennie Z. Young, Fan Gao, Manolis Kellis, Li-Huei Tsai

Issue&Volume: 2020-10-05

Abstract: The epigenome and three-dimensional (3D) genomic architecture are emerging as key factors in the dynamic regulation of different transcriptional programs required for neuronal functions. In this study, we used an activity-dependent tagging system in mice to determine the epigenetic state, 3D genome architecture and transcriptional landscape of engram cells over the lifespan of memory formation and recall. Our findings reveal that memory encoding leads to an epigenetic priming event, marked by increased accessibility of enhancers without the corresponding transcriptional changes. Memory consolidation subsequently results in spatial reorganization of large chromatin segments and promoter–enhancer interactions. Finally, with reactivation, engram neurons use a subset of de novo long-range interactions, where primed enhancers are brought in contact with their respective promoters to upregulate genes involved in local protein translation in synaptic compartments. Collectively, our work elucidates the comprehensive transcriptional and epigenomic landscape across the lifespan of memory formation and recall in the hippocampal engram ensemble. The authors show that a coordinated epigenetic priming event during memory encoding and consolidation facilitates promoter–enhancer interactions that are vital for the unique transcriptional output of reactivated engram neurons.

DOI: 10.1038/s41593-020-00717-0

Source: https://www.nature.com/articles/s41593-020-00717-0

期刊信息

Nature Neuroscience:《自然—神经科学》,创刊于1998年。隶属于施普林格·自然出版集团,最新if:21.126
官方网址:https://www.nature.com/neuro/
投稿链接:https://mts-nn.nature.com/cgi-bin/main.plex